Our long term goal of this program is to develop nanoarrays as highly-specific, highly-sensitive and ultrahigh-throughput platforms in mass spectrometry for proteomic and metabolomic applications. This will be built upon the close collaborations of 2 laboratories with complementary expertise: Wang (LBNL) in mass spectrometry and proteomics, and Yang (LBNL/UC Berkeley) in nanoscience and nanotechnology. Proteomics and metabolomics as integral systems biology components will generate a new knowledgebase for hypothesis-driven biochemical and bioimaging studies. Further developments in the enabling technology- mass spectrometry-are required to significantly increase the sensitivity and dynamic range. Revolutionary innovations are needed to ultimately achieve proteomics and metabolomics of single cells. Nanostructures are structures defined as having at least 1 dimension at nanometer scale, and have generated intensive interests as a result of their fascinating properties, and unique applications superior to their bulk counterparts. Exciting opportunities exist by making new types of nanostructures or simply by shrinking the size of existing microstructures into the nanometer regime. In this exploratory/ developmental R21 project, we propose to develop novel nanoarray-based substrates for mass spectrometry and demonstrate their applications in proteomics and metabolomics. Specifically we propose to develop a new kind of ionization source. We will take a multi-faceted approach to fabricate and characterize the devices (Aim 1), elucidate the ionization mechanisms (Aim 2), and demonstrate the proof-of-principle applications in mass spectrometry for single stem cell proteomics (Aim 3). Our extensive capabilities and expertise in the fabrication of nanowire and nanotube arrays, and in the integration of nanodevices and microdevices, will put us in a unique position to achieve potential breakthroughs. If successful, these nano devices will serve as a critical component in the nanofluidics and microfluidics structures to separate, detect, and identify biomolecules, and open up new possibilities in systems biology. Relevance to public health: Stem cells can self-renew and show great promise in regenerative medicine. Revolutionary innovations are needed to ultimately elucidate stem cell differentiation at single cell level. Towards this goal, we propose to utilize the enormous potential of nanotechnology to develop novel ionization substrates for mass spectrometry to study proteins and metabolites of single stem cells. [unreadable] [unreadable] [unreadable]